The metabolism of cis-dichlorodiammineplatinum (II): distribution, clearance, and toxicity

The distribution and toxicity of 195mPt-labeled cis-platinum were studied in two groups of dogs. Serum and tissue levels, renal and marrow toxicities, and urinary excretion were compared in dogs given cis-platinum, 3 mg/kg, intravenously with a group treated by intraperitoneal administration. Peak serum levels occurred immediately after intravenous administration and 8 hours after intraperitoneal instillation, at which time the two were identical and declined at similar rates. Mean levels of cis-platinum measured in peritoneal tissues on day 4 were higher in the intraperitoneal group. Blood urea nitrogen, creatinine, and white blood cell and platelet counts were similar in both groups. Bloody ascites and adhesion formation occurred in 37.5% of dogs treated by intraperitoneal administration. The intraperitoneal route of chemotherapy administration results in higher drug levels in target peritoneal tissues without a corresponding increase in systemic toxicity.